Acute Toxicity of Hypofractionated and Conventionally Fractionated (Chemo)Radiotherapy Regimens for Bladder Cancer: An Exploratory Analysis from the RAIDER Trial.

AIMS: Adding concurrent (chemo)therapy to radiotherapy improves outcomes for muscle-invasive bladder cancer patients. A recent meta-analysis showed superior invasive locoregional disease control for a hypofractionated 55 Gy in 20 fractions schedule compared with 64 Gy in 32 fractions. In the RAIDER clinical trial, patients undergoing 20 or 32 fractions of radical radiotherapy were randomised (1:1:2) to standard radiotherapy or to standard-dose or escalated-dose adaptive radiotherapy. Neoadjuvant chemotherapy and concomitant therapy were permitted. We report exploratory analyses of acute toxicity by concomitant therapy-fractionation schedule combination. MATERIALS AND METHODS: Participants had unifocal bladder urothelial carcinoma staged T2-T4a N0 M0. Acute toxicity was assessed (Common Terminology Criteria for Adverse Events) weekly during radiotherapy and at 10 weeks after the start of treatment. Within each fractionation cohort, non-randomised comparisons of the proportion of patients reporting treatment emergent grade 2 or worse genitourinary, gastrointestinal or other adverse events at any point in the acute period were carried out using Fisher's exact tests. RESULTS: Between September 2015 and April 2020, 345 (163 receiving 20 fractions; 182 receiving 32 fractions) patients were recruited from 46 centres. The median age was 73 years; 49% received neoadjuvant chemotherapy; 71% received concomitant therapy, with 5-fluorouracil/mitomycin C most commonly used: 44/114 (39%) receiving 20 fractions; 94/130 (72%) receiving 32 fractions. The acute grade 2+ gastrointestinal toxicity rate was higher in those receiving concomitant therapy compared with radiotherapy alone in the 20-fraction cohort [54/111 (49%) versus 7/49 (14%), P < 0.001] but not in the 32-fraction cohort (P = 0.355). Grade 2+ gastrointestinal toxicity was highest for gemcitabine, with evidence of significant differences across therapies in the 32-fraction cohort (P = 0.006), with a similar pattern but no significant differences in the 20-fraction cohort (P = 0.099). There was no evidence of differences in grade 2+ genitourinary toxicity between concomitant therapies in either the 20- or 32-fraction cohorts. CONCLUSION: Grade 2+ acute adverse events are common. The toxicity profile varied by type of concomitant therapy; the gastrointestinal toxicity rate seemed to be higher in patients receiving gemcitabine.

Faecal microbiota transplantation for treatment of recurrent or refractory Clostridioides difficile infection in Hong Kong.

INTRODUCTION: Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated infection globally, causing significant morbidity and mortality. Faecal microbiota transplantation (FMT) has emerged as a promising option for recurrent and refractory CDI. This study aimed to assess the safety, efficacy, and feasibility of FMT for CDI in Hong Kong. METHODS: We conducted a single-centre, retrospective study for all consecutive cases of recurrent or refractory CDI who underwent FMT from 2013 to 2018. Clinical demographics, outcome, and safety parameters were collected. RESULTS: A total of 24 patients with recurrent or refractory CDI (median age 70 years, interquartile range=45.0-78.3 years; 67% male) were included. Over 80% had been recently hospitalised or were long-term care facility residents. Faecal microbiota transplantation was delivered by feeding tube in 11 (45.8%), oesophagogastroduodenoscopy in eight (33.3%), and colonoscopy in six (25%) of the patients. Resolution of diarrhoea without relapse within 8 weeks was achieved in 21 out of 24 patients (87.5%) after FMT. No deaths occurred within 30 days. The FMT was well tolerated and no serious adverse events attributable to FMT were reported. CONCLUSION: Our results confirm that FMT is a safe, efficacious, and feasible intervention for patients with refractory or recurrent CDI in Hong Kong. Given the increasing disease burden and the lack of effective alternatives in Hong Kong for difficult-to-treat cases of CDI, we recommend that a territory-wide FMT service be established to address increasing demand for this treatment.

Implementing Pharmacogenomics in Europe: Design and Implementation Strategy of the Ubiquitous Pharmacogenomics Consortium.

Despite scientific and clinical advances in the field of pharmacogenomics (PGx), application into routine care remains limited. Opportunely, several implementation studies and programs have been initiated over recent years. This article presents an overview of these studies and identifies current research gaps. Importantly, one such gap is the undetermined collective clinical utility of implementing a panel of PGx-markers into routine care, because the evidence base is currently limited to specific, individual drug-gene pairs. The Ubiquitous Pharmacogenomics (U-PGx) Consortium, which has been funded by the European Commission's Horizon-2020 program, aims to address this unmet need. In a prospective, block-randomized, controlled clinical study (PREemptive Pharmacogenomic testing for prevention of Adverse drug REactions [PREPARE]), pre-emptive genotyping of a panel of clinically relevant PGx-markers, for which guidelines are available, will be implemented across healthcare institutions in seven European countries. The impact on patient outcomes and cost-effectiveness will be investigated. The program is unique in its multicenter, multigene, multidrug, multi-ethnic, and multihealthcare system approach.

Combined effects of land reclamation, channel dredging upon the bioavailable concentration of polycyclic aromatic hydrocarbons (PAHs) in Victoria Harbour sediment, Hong Kong.

The up-to-date concentration of polycyclic aromatic hydrocarbons (PAHs) in sediment materials of Victoria Harbour was investigated so as to evaluate the pollution potential associated with the reclamation projects in Hong Kong. A total of 100 sediment samples were collected at 20 locations. Except the control point in reservoir, the PAHs concentrations were detectable levels all sites (131-628.3ng/g, dw) and such values were higher than Dutch Target and Intervention Values (the New Dutch standard in 2016). The PAHs concentration indicating that construction waste and wastewater discharges were the main pollutant sources. Results of correlation in single cell gel electrophoresis assay (comet assay) studies also revealed that the PAHs concentration was highly correlated (<0.01) with DNA migration (i.e. the length of tail moment of fish cells) in 5mg/ml of PAHs. The above observation indicates that the PAHs present in the sediment may substantially effect the marine ecosystem. Although the dredged sediment can be a useful sea-filling material for land reclamation; however, the continuing leaching of PAHs and its impact on the aquatic environment need to be studied further.

Monitoring and assessment of heavy metal contamination in a constructed wetland in Shaoguan (Guangdong Province, China): bioaccumulation of Pb, Zn, Cu and Cd in aquatic and terrestrial components.

The objective of this study is to evaluate the current status of heavy metal concentrations in constructed wetland, Shaoguan (Guangdong, China). Sediments, three wetland plants (Typha latifolia, Phragmites australis, and Cyperus malaccensis), and six freshwater fish species [Carassius auratus (Goldfish), Cirrhinus molitorella (Mud carp), Ctenopharyngodon idellus (Grass carp), Cyprinus carpio (Wild common carp), Nicholsicypris normalis (Mandarin fish), Sarcocheilichthys kiangsiensis (Minnows)] in a constructed wetland in Shaoguan were collected and analyzed for their heavy metal compositions. Levels of Pb, Zn, Cu, and Cd in sediments exceeded approximately 532, 285, 11, and 66 times of the Dutch Intervention value. From the current study, the concentrations of Pb and Zn in three plants were generally high, especially in root tissues. For fish, concentrations of all studied metals in whole body of N. mormalis were the highest among all the fishes investigated (Pb 113.4 mg/kg, dw; Zn 183.1 mg/kg, dw; Cu 19.41 mg/kg, dw; 0.846 mg/kg, dw). Heavy metal accumulation in different ecological compartments was analyzed by principle component analysis (PCA), and there is one majority of grouped heavy metals concentration as similar in composition of ecological compartment, with the Cd concentration quite dissimilar. In relation to future prospect, phytoremediation technology for enhanced heavy metal accumulation by constructed wetland is still in early stage and needs more attention in gene manipulation area.

On-chip clearing of arrays of 3-D cell cultures and micro-tissues.

Three-dimensional (3-D) cell cultures are beneficial models for mimicking the complexities of in vivo tissues, especially in tumour studies where transport limitations can complicate response to cancer drugs. 3-D optical microscopy techniques are less involved than traditional embedding and sectioning, but are impeded by optical scattering properties of the tissues. Confocal and even two-photon microscopy limit sample imaging to approximately 100-200 µm depth, which is insufficient to image hypoxic spheroid cores. Optical clearing methods have permitted high-depth imaging of tissues without physical sectioning, but they are difficult to implement for smaller 3-D cultures due to sample loss in solution exchange. In this work, we demonstrate a microfluidic platform for high-throughput on-chip optical clearing of breast cancer spheroids using the SeeDB, Clear(T2), and ScaleSQ clearing methods. Although all three methods are able to effectively clear the spheroids, we find that SeeDB and ScaleSQ more effectively clear the sample than Clear(T2); however, SeeDB induces green autofluorescence while ScaleS causes sample expansion. Our unique on-chip implementation permits clearing arrays of 3-D cultures using perfusion while monitoring the 3-D cultures throughout the process, enabling visualization of the clearing endpoint as well as monitoring of transient changes that could induce image artefacts. Our microfluidic device is compatible with on-chip 3-D cell culture, permitting the use of on-chip clearing at the endpoint after monitoring the same spheroids during their culture. This on-chip method has the potential to improve readout from 3-D cultures, facilitating their use in cell-based assays for high-content drug screening and other applications.

Core-shell hydrogel beads with extracellular matrix for tumor spheroid formation.

Creating multicellular tumor spheroids is critical for characterizing anticancer treatments since they may provide a better model of the tumor than conventional monolayer culture. Moreover, tumor cell interaction with the extracellular matrix can determine cell organization and behavior. In this work, a microfluidic system was used to form cell-laden core-shell beads which incorporate elements of the extracellular matrix and support the formation of multicellular spheroids. The bead core (comprising a mixture of alginate, collagen, and reconstituted basement membrane, with gelation by temperature control) and shell (comprising alginate hydrogel, with gelation by ionic crosslinking) were simultaneously formed through flow focusing using a cooled flow path into the microfluidic chip. During droplet gelation, the alginate acts as a fast-gelling shell which aids in preventing droplet coalescence and in maintaining spherical droplet geometry during the slower gelation of the collagen and reconstituted basement membrane components as the beads warm up. After droplet gelation, the encapsulated MCF-7 cells proliferated to form uniform spheroids when the beads contained all three components: alginate, collagen, and reconstituted basement membrane. The dose-dependent response of the MCF-7 cell tumor spheroids to two anticancer drugs, docetaxel and tamoxifen, was compared to conventional monolayer culture.

Comparative assessment of water quality parameters of mariculture for fish production in Hong Kong Waters.

The objective of the study is to evaluate the effect of fish cultivation on water quality in fish culture zone (FCZ) and analysed by Principle Component Analysis (PCA). 120 surface water samples were collected from Hong Kong Waters (60 samples in Victoria Harbour and another 60 in Ma Wan FCZ). Significant difference was found in dissolved oxygen (MW: 59.6%; VH: 81.3%), and Escherichia coli (MW: 465 CFU/100 ml; VH: 162.5 CFU/100 ml). Three principle components are responsible for water quality variations in the studying sites. The first component included E. coli (0.625) and dissolved oxygen (0.701). The second included E. coli (0.387) and ammonical-nitrogen (0.571). The third included E. coli (0.194) and ammonical-nitrogen (0.287). This framework provides information to assess the relative contribution of eco-aquaculture to nutrient loads and the subsequent risk of eutrophication. To conclude, a rigorous monitoring of water quality is necessary to assess point and nonpoint source pollution. Besides, appropriate remediation techniques should be used to combat water pollution and achieve sustainability.

Fabrication and laser patterning of polystyrene optical oxygen sensor films for lab-on-a-chip applications.

We present a novel and simple method for patterning oxygen-sensitive polystyrene thin films and demonstrate its potential for integration with microfluidic lab-on-a-chip devices. Optical oxygen sensing films composed of polystyrene with an embedded luminescent oxygen-sensitive dye present a convenient option for the measurement of oxygen levels in microfluidic and lab-on-a-chip devices; however, patterning and integrating the films with poly(dimethylsiloxane) (PDMS) microfluidic devices has proven difficult due to a residue after dry etch patterning that inhibits subsequent PDMS bonding. Our new method uses mask-less laser ablation by a commercial laser ablation system to define the outline of the structures and subsequent bulk film removal by aqueous lift-off. Because the bulk film is peeled or lifted off of the substrate rather than etched, the process is compatible with standard PDMS plasma bonding. We used ToF-SIMS analysis to investigate how laser ablation facilitates this fabrication process as well as why dry etching polystyrene inhibits PDMS plasma bonding. The results of this analysis showed evidence of chemical species formed during the laser ablation and dry etching processes that can produce these effects. Our new method's mask-less nature, simplicity, speed, and compatibility with PDMS bonding make it ideally suited for single-use lab-on-a-chip applications. To demonstrate the method's compatibility with PDMS microfluidics, we also present a demonstration of the sensors' integration into a microfluidic oxygen gradient generator device.

Assessment of heavy metals/metalloid (As, Pb, Cd, Ni, Zn, Cr, Cu, Mn) concentrations in edible fish species tissue in the Pearl River Delta (PRD), China.

The major aim of this study was to investigate heavy metal content of edible fish in the PRD. Eleven species of fish (consisting of 711 individuals) [catfish (Clarias fuscus), tilapia (Oreochromis mossambicus), grass carp (Ctenopharyngodon idellus), bighead carp (Aristichthys nobilis), mandarin fish (Siniperca kneri), snakehead (Channa asiatiea), black bass (Micropterus salmoides), mangrove snapper (Lutjanus griseus), star snapper (Lutjanu stellatus), snubnose pompano (Trachinotus blochii) and orange-spotted grouper (Epinephelus coioides)] were collected for the analyses of heavy metals. Overall concentrations (mg/kg, ww) in the fish muscles were: As (0.03-1.53), Pb (0.03-8.62), Cd (0.02-0.06), Ni (0.44-9.75), Zn (15.7-29.5), Cr (0.22-0.65), Cu (0.79-2.26), Mn (0.82-6.91). Significant level of Pb were found in tilapia at all locations. It is recommended that heavy metal concentrations in different fish species must be determined on a regular basis in the future so as to reduce human health risks from acute and chronic food intoxication.

Mixed arbuscular mycorrhizal (AM) fungal application to improve growth and arsenic accumulation of Pteris vittata (As hyperaccumulator) grown in As-contaminated soil.

A greenhouse pot experiment was conducted to study the effects of three types of single inoculum [indigenous mycorrhizas (IM) isolated from As mine, Glomus mosseae (GM) and Glomus intraradices (GI)] and two types of mixed inoculum (mixed with IM and either GM or GI) on the growth response of Pteris vittata (hyperaccumulator) and Cynodon dactylon (non-hyperaccumulator) at three levels of As concentrations (0, 100 and 200mgkg(-1)). Both mycorrhizal plants exhibited significantly higher biomass, and N and P accumulation in its tissue than the control. Among the mycorrhizal inoculum, the mixed inoculum IM/GM promoted substantially higher mycorrhizal colonization and arsenate reductase activity in P. vittata than C. dactylon, among all As levels. The portion of Paris arbuscular mycorrhizal structure (observed in colonized roots) together with the highest As translocation factor of 10.2 in P. vittata inoculated with IM/GM was also noted. It was deduced that IM/GM inoculum may be the best choice for field inoculation at any contaminated lands as the inoculum exhibited better adaptation to variable environmental conditions and hence benefited the host plants.

Synergistic effects of arbuscular mycorrhizal fungi and phosphate rock on heavy metal uptake and accumulation by an arsenic hyperaccumulator.

The effects of arbuscular mycorrhizal (AM) fungi and phosphate rock on the phytorextraction efficiency of a hyperaccumulator (Pteris vittata) and a non-hyperaccumulator (Cynodon dactylon) plant were studied. Both seedlings were planted in As contaminated soil under different treatments [(1) control (contaminated soil only), (2) indigenous mycorrhizas (IM), (3) mixed AM inoculum [indigenous mycorrhiza + Glomus mosseae (IM/Gm)] and (4) IM/Gm + phosphate rock (P rock)] with varying intensities (40%, 70% and 100%) of water moisture content (WMC). Significant As reduction in soil (23.8% of soil As reduction), increase in plant biomass (17.8 g/pot) and As accumulation (2054 mg/kg DW) were observed for P. vittata treated with IM/Gm + PR at 100% WMC level. The overall results indicated that the synergistic effect of mycorrhiza and P rock affected As subcellular distribution of the hyperaccumulator and thereby altered its As removal efficiency under well-watered conditions.

Risk assessment of residual DDTs in freshwater and marine fish cultivated around the Pearl River Delta, China.

Six species of freshwater fish collected from 10 fishponds in Shunde and Zhongshan, China, four species of marine fishes collected from different mariculture farms [four in Hong Kong (Tung Lung Chau, Ma Wan, Cheung Chau and Kat O) and two in mainland China (Daya Bay and Shenzhen)] together with feed (both trash fish and commercial pellets) and sediment were analyzed for DDTs. Total DDTs in freshwater fish flesh decreased in the order of: carnivores [1742 microg/kg lipid weight (l.w.)] > herbivores (165 microg/kg, l.w.) > omnivores (42.5 microg/kg, l.w.), with the highest concentration detected in mandarin fish (Siniperca chuatsi) (2641 microg/kg, l.w.). For marine fish, snubnose pompano (Trachinotus blochii) and orange-spotted grouper (Epinephelus coioides) collected in Ma Wan contained elevated levels of total DDTs (2590 and 2034 microg/kg l.w., respectively). Trash fish used in both freshwater and marine fish farms contained significantly higher levels (86.5-641 microg/kg l.w.) (p < 0.05) of DDTs than in commercial pellets, but correlations between DDT levels in fish feed and muscle were not significant. The elevated biota-sediment accumulating factor for tilapia (Tilapia mossambicus) (24.1) indicated that accumulation of DDTs from sediment to the fish was evident. It can be concluded that trash fish should not be used for fish culture in order to lower the level of residual DDTs in fish muscle.

Adsorption kinetics of Pb and Cd by two plant growth promoting rhizobacteria.

A bench study was carried out to characterize the kinetics of two plant growth promoting rhizobacteria (PGPR) Azotobacter chroococcum and Bacillus megaterium to adsorb heavy metals from solution. Adsorption of Pb(2+) and Cd(2+) by bacterial cells was processed quickly with an equilibration achieved within 5 min. The adsorptions were fitted well with Freundlich and Langmuir isotherm models. The comparison of isotherm parameters indicated that A. chroococcum had a stronger capacity to bind metal ions than B. megaterium, with an average increase of 59.8% for Pb(2+) and 75.6% for Cd(2+), respectively. Both bacteria had a stronger affinity to Pb(2+) than Cd(2+) since Pb(2+) was more easily bound with the phosphoryl groups on the cell surface than Cd(2+). This demonstrated that the presence of bacteria in the rhizosphere may result in the reduction of mobile ions in soil solution.

Phase contrast imaging of breast tumours with synchrotron radiation.

Even though the potential of phase contrast (PC) imaging has been demonstrated in a number of biological tissue samples, the availability of free-space propagation phase contrast images of real breast tumours is still limited. The aim of this study was to obtain phase contrast images of two different pathological breast specimens containing tumours of differing morphological type at two synchrotron radiation (SR) facilities, and to assess any qualitative improvements in the evaluation and characterisation of the masses through the use of phase contrast imaging. A second aim was to assess the effects of parameters such as detector resolution, beam energy and sample-to-detector distance on image quality using the same breast specimens, as to date these effects have been modelled and discussed only for geometric phantoms. At each synchrotron radiation facility a range of images was acquired with different detectors and by varying the above parameters. Images of the same samples were also acquired with the absorption-based approach to allow a direct comparison and estimation of the advantages specifically ascribable to the PC technique.

Microfluidic system for controlled gelation of a thermally reversible hydrogel.

The integration of cell culture and characterization onto a miniaturized platform promises to benefit many applications such as tissue engineering, drug screening, and those involving small, precious cell populations. This paper presents the controlled on-chip gelation of a thermally-reversible hydrogel. Channel design and flowrate control are crucial in determining hydrogel geometry, while integrated temperature control triggers reversible gel formation. Formation of hydrogel droplets through shearing of immiscible flows is demonstrated with subsequent on-chip gelation. The temperature of phase transition occurs between 32degC-34degC, well within the range for mammalian cell encapsulation and culture.

Physiological and biochemical responses of rice (Oryza sativa L.) to phenanthrene and pyrene.

Phenanthrene (Phe) and pyrene (Pyr) are two typical polycyclic aromatic hydrocarbons (PAHs) found in contaminated soil. This study investigated physiological and biochemical responses of rice (Oryza sativa L.) to PAH stress after they were planted in soils contaminated with Phe and Pyr, in the presence or absence of a PAH-degrading bacteria (Acinetobacteria sp.). A number of parameters including biomass and water, chlorophyll and chlorophyll a/b ratio, electrolyte leakage, activities of superoxide dismutase (SOD) and peroxidase, and soluble carbohydrate and soluble protein contents were monitored. Results show that rice plants have good resistance and tolerance to lower levels of PAHs stress, while adding high levels of PAHs to soils resulted in adverse effects on rice plants such as a reduction in biomass and damage to photosynthetic function. Water content and SOD activities were the most sensitive indicators of PAH stress among the observed parameters. Inoculation with PAH-degrading bacteria promoted growth and photosynthesis of rice.

Heavy metals concentrations of surface dust from e-waste recycling and its human health implications in southeast China.

The recycling of printed circuit boards in Guiyu, China, a village intensely involved in e-waste processing, may present a significant environmental and human health risk. To evaluate the extent of heavy metals (Cd, Co, Cr, Cu, Ni, Pb, Zn) contamination from printed circuit board recycling, surface dust samples were collected from recycling workshops, adjacent roads, a schoolyard, and an outdoor food market. ICP-OES analyses revealed elevated mean concentrations in workshop dust (Pb 110,000, Cu 8360, Zn 4420, and Ni 1500 mg/kg) and in dust of adjacent roads (Pb 22,600, Cu 6170, Zn 2370, and Ni 304 mg/kg). Lead and Cu in road dust were 330 and 106, and 371 and 155 times higher, respectively, than non e-waste sites located 8 and 30 km away. Levels at the schoolyard and food market showed that public places were adversely impacted. Risk assessment predicted that Pb and Cu originating from circuit board recycling have the potential to pose serious health risks to workers and local residents of Guiyu, especially children, and warrants an urgent investigation into heavy metal related health impacts. The potential environmental and human health consequences due to uncontrolled e-waste recycling in Guiyu serves as a case study for other countries involved in similar crude recycling activities.